In this study, ADR and alpha variability could detect DCI development before ischemic changes on CT scan was apparent and before clinical deterioration was noted. Implementation of cEEG in aSAH patients can probably improve early detection of DCI.

This study shows a trend towards less extensive axillary surgery in Dutch cT1-T4N0M0 breast cancer patients; illustrated by an overall increase of sentinel lymph node biopsy and decrease in cALND. Despite this trend, particularly noticed in cT1-2N0 sentinel node-positive patients after publication of the ACOSOG-Z0011 and AMAROS trial, variations in patterns of care in axillary surgery are still present.

WHAT THIS STUDY ADDS This systematic review presents an overview of the available evidence on patient related features associated with an increased susceptibility to the development of new ischaemic brain lesions on magnetic resonance diffusion weighted imaging after carotid endarterectomy and carotid artery stenting. These demographic, radiological, and biochemical predictors may be helpful in decision making on patient selection for medical intervention, carotid stenting, or endarterectomy.Objectives: Peri-procedural ischaemic brain lesions on diffusion weighted imaging (DWI) after carotid endarterectomy (CEA) and carotid artery stenting (CAS) have been related to a higher chance of recurrent cerebrovascular events. This systematic review provides an overview of patient characteristics associated with increased risk of new DWI lesions. Methods: MEDLINE, EMBASE, and Cochrane library databases were systematically searched (update November 2018) for studies reporting post-procedural DWI lesions after CEA or CAS. Data derived from both procedures were analysed separately. Studies reporting predictive features that were present prior to intervention were assigned to 10 categories: age, gender, cardiovascular risk factors, symptomatology, plaque vulnerability, atherosclerotic burden, cerebrovascular haemodynamics, carotid/arch anatomy, inflammatory markers, and markers of coagulation. A semi-quantitative analysis was performed by plotting studies that found an association between the investigated features and DWI lesions against those that did not find an association. Results: Forty-six studies (5018 patients) were included: 10 reported only CEA, 33 CAS, and three both interventions. 68.0% of 1873 CEA patients and 55.9% of 3145 CAS patients were symptomatic. The weighted prevalence of DWI lesions was 18.1% (95% CI 14.0e22.7%) in CEA patients compared with 40.5% (95% CI 35.4e45.7%) in CAS patients. Studies reporting on CEA patients predominantly found an increased risk in symptomatic patients (two of seven studies, including 848/1661 patients), those with impaired haemodynamics (five of five studies), and increased inflammatory markers (two of three studies). Studies reporting on CAS patients often found a positive association with age (10/26 studies), high plaque vulnerability (25/34 studies), or complex carotid/arch anatomy (three out of five studies). Conclusions: For patients undergoing CEA, symptomatic status, impeded cerebral haemodynamics, and increased inflammatory markers are associated with increased susceptibility to peri-operative DWI lesions. In CAS patients, higher age, plaque vulnerability and complex carotid/aortic arch anatomy were identified as risk factors. These clinical predictors may assist with decision making on patient selection for medical treatment, CEA or CAS.

Recently, a focus on the timing of intervention, as well as improvements in medical therapy, have changed the clinical treatment algorithm of carotid revascularisation. The debate remains alive when it comes to the optimal treatment strategy, including early (<14 days) vs. expedited (<48 h) revascularisation, the role of plaque vulnerability in decision making, and alternative (endovascular) revascularisation approaches. In weighing up the relative contribution and relevance of these strategies on outcome, it is of utmost importance to apply universally accepted and clear endpoints. As the classic clinical endpoints of "procedural

Objectives: Peri-procedural ischaemic brain lesions on diffusion weighted imaging (DWI) after carotid endarterectomy (CEA) and carotid artery stenting (CAS) have been related to a higher chance of recurrent cerebrovascular events. This systematic review provides an overview of patient characteristics associated with increased risk of new DWI lesions. Methods: MEDLINE, EMBASE, and Cochrane library databases were systematically searched (update November 2018) for studies reporting postprocedural DWI lesions after CEA or CAS. Data derived from both procedures were analysed separately. Studies reporting predictive features that were present prior to intervention were assigned to 10 categories: age, gender, cardiovascular risk factors, symptomatology, plaque vulnerability, atherosclerotic burden, cerebrovascular haemodynamics, carotid/arch anatomy, inflammatory markers, and markers of coagulation. A semiquantitative analysis was performed by plotting studies that found an association between the investigated features and DWI lesions against those that did not find an association. Results: Forty-six studies (5018 patients) were included: 10 reported only CEA, 33 CAS, and three both interventions. 68.0% of 1873 CEA patients and 55.9% of 3145 CAS patients were symptomatic. The weighted prevalence of DWI lesions was 18.1% (95% CI 14.0e22.7%) in CEA patients compared with 40.5% (95% CI 35.4e45.7%) in CAS patients. Studies reporting on CEA patients predominantly found an increased risk in symptomatic patients (two of seven studies, including 848/1661 patients), those with impaired haemodynamics (five of five studies), and increased inflammatory markers (two of three studies). Studies reporting on CAS patients often found a positive association with age (10/26 studies), high plaque vulnerability (25/34 studies), or complex carotid/arch anatomy (three out of five studies). Conclusions: For patients undergoing CEA, symptomatic status, impeded cerebral haemodynamics, and increased inflammatory markers are associated with increased susceptibility to peri-operative DWI lesions. In CAS patients, higher age, plaque vulnerability and complex carotid/aortic arch anatomy were identified as risk factors. These clinical predictors may assist with decision making on patient selection for medical treatment, CEA or CAS.

WHAT THIS PAPER ADDSThis study investigated peri-operative blood pressure (BP) in patients undergoing carotid endarterectomy and its relationship with post-operative ischaemic brain lesions on magnetic resonance diffusion weighted imaging (DWI). There is increasing insight into the clinical relevance of DWI lesions, but little is known about the predictive, causative factors. This is the first study into the relationship between new DWI lesions (ipsi-or contralateral) and pre-operative vs. intra-operative BP. The results imply that patients with pre-operative hypertension are susceptible to intra-operative haemodynamic instability and development of silent DWI lesions. These data may affect future protocols for peri-operative haemodynamic regulation.Objective: Intra-operative haemodynamic instability during carotid endarterectomy (CEA) has been associated with an increased risk of procedural stroke. Diffusion weighted imaging (DWI) lesions have been proposed as a surrogate marker for peri-operative silent cerebral ischaemia. This study aimed to investigate the relationship between peri-operative blood pressure (BP) and presence of post-operative DWI lesions in patients undergoing CEA. Methods: A retrospective analysis was performed based on patients with symptomatic CEA included in the MRI substudy of the International Carotid Stenting Study. Relative intra-operative hypotension was defined as a decrease of intra-operative systolic BP ! 20% compared with pre-operative ('baseline') BP, absolute hypotension was defined as a drop in systolic BP < 80 mmHg. The primary endpoint was the presence of any new DWI lesions on postoperative MRI (DWI positive). The occurrence and duration of intra-operative hypotension was compared between DWI positive and DWI negative patients as was the magnitude of the difference between pre-and intra-operative BP. Results: Fifty-five patients with symptomatic CEA were included, of whom eight were DWI positive. DWI positive patients had a significantly higher baseline systolic (186 AE 31 vs. 158 AE 27 mmHg, p ¼ .011) and diastolic BP (95 AE 15 vs. 84 AE 13 mmHg, p ¼ .046) compared with DWI negative patients. Other pre-operative characteristics did not differ. Relative intra-operative hypotension compared with baseline occurred in 53/55 patients (median duration 34 min; range 0e174). Duration of hypotension did not differ significantly between the groups (p ¼ .088). Mean systolic intra-operative BP compared with baseline revealed a larger drop in BP (À37 AE 29 mmHg) in DWI positive compared with DWI negative patients (À14 AE 26 mmHg, p ¼ .024). Absolute intra-operative systolic BP values did not differ between the groups. Conclusion: In this exploratory study, high pre-operative BP and a larger drop of intra-operative BP were associated with peri-procedural cerebral ischaemia as documented with DWI. These results call for confirmation in an adequately sized prospective study, as they suggest important consequences for perioperative haemodynamic management in carotid revascularisation.

WHAT THIS PAPER ADDSThis study investigated the clinical relevance of reported cerebral small vessel disease (SVD, including white matter lesions and lacunar infarcts) for post-operative stroke and death risk in symptomatic patients undergoing carotid endarterectomy (CEA). The study highlights that the presence of SVD in standard routine pre-operative brain imaging reports identifies patients at high risk of cardiovascular death. Yet, reported SVD is not associated with procedural or long term post-operative stroke risk and therefore this should not influence the decision whether CEA should be performed in symptomatic patients with high degree carotid artery stenosis.Objective: Cerebral white matter lesions (WMLs) and lacunar infarcts are surrogates of cerebral small vessel disease (SVD). WML severity as determined by trained radiologists predicts post-operative stroke or death in patients undergoing carotid endarterectomy (CEA). It is unknown whether routine pre-operative brain imaging reports as part of standard clinical practice also predict short and long term risk of stroke and death after CEA. Methods: Consecutive patients from the Athero-Express biobank study that underwent CEA for symptomatic high degree stenosis between March 2002 and November 2014 were included. Pre-operative brain imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) reports were reviewed for reporting of SVD, defined as WMLs or any lacunar infarcts. The primary outcome was defined as any stroke or any cardiovascular death over three year follow up. The secondary outcome was defined as the 30 day perioperative risk of stroke or cardiovascular death. Results: A total of 1038 patients were included (34% women), of whom 659 (63.5%) had CT images and 379 (36.5%) MRI images available. Of all patients, 697 (67%) had SVD reported by radiologists. Patients with SVD had a higher three year risk of cardiovascular death than those without (6.5% vs. 2.1%, adjusted HR 2.52 [95% CI 1.12e5.67]; p ¼ .026) but no association was observed for the three year risk of stroke (9.0% vs. 6.7%, for patients with SVD vs. those without, adjusted HR 1.24 [95% CI 0.76e2.02]; p ¼ .395). No differences in 30 day peri-operative risk were observed for stroke (4.4% vs. 2.9%, for patients with vs. those without SVD; adjusted HR 1.49 [95% CI 0.73e3.05]; p ¼ .28), and for the combined stroke/cardiovascular death risk (4.4% vs. 3.5%, adjusted HR 1.20 [95% CI 0.61e2.35]; p ¼ .59). Conclusion: Presence of SVD in pre-operative brain imaging reports can serve as a predictor for the three year risk of cardiovascular death in symptomatic patients undergoing CEA but does not predict peri-operative or long term risk of stroke.

We aimed to investigate the effect of chronic cerebral hypoperfusion on cerebral hemodynamics and perivascular nerve density in a rat model. Bilateral common carotid artery (CCA) ligation (n = 24) or sham‐operation (n = 24) was performed with a 1‐week interval. A subgroup (ligated n = 6; sham‐operated n = 3) underwent magnetic resonance imaging (MRI) before the procedures and 2 and 4 weeks after the second procedure. After termination, carotids were harvested for assessment of complete ligation and nerve density in cerebral arteries that were stained for the general neural marker PGP 9.5 and sympathetic marker TH by computerized image analysis. Five rats were excluded because of incomplete ligation. MRI‐based tortuosity of the posterior communicating artery (Pcom), first part of the posterior cerebral artery (P1) and basilar artery was observed in the ligated group, as well as an increased volume (p = 0.05) and relative signal intensity in the basilar artery (p = 0.04; sham‐group unchanged). Immunohistochemical analysis revealed that compared to sham‐operated rats, ligated rats had increased diameters of all intracircular segments and the extracircular part of the internal carotid artery (p < 0.05). Ligated rats showed a higher general nerve density compared to controls in P1 (10%, IQR:8.7–10.5 vs. 6.6%, IQR:5.5–7.4, p = 0.003) and Pcom segments (6.4%, IQR:5.8–6.5 vs. 3.2%, IQR:2.4–4.3, p = 0.003) and higher sympathetic nerve density in Pcom segments (3.7%, IQR:2.8–4.8 vs. 1.7%, IQR:1.3–2.2, p = 0.02). Bilateral CCA occlusion resulted in redistribution of blood flow to posteriorly located cerebral arteries with remarkable changes in morphology and perivascular nerve density, suggesting a functional role for perivascular nerves in cerebral autoregulation.